3-Bromophenol → 3-(4-bromo-2-hydroxyphenyl)-3-hydroxy-1-{[5-(trifluoromethyl)furan-2-yl]methyl}-1,3-dihydro-2H-indol-2-one

HRID 1407374Notes

Reaction equation

HRID 1407374 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.C([Mg]Cl)(C)C.[F:14][C:15]([F:34])([F:33])[C:16]1[O:20][C:19]([CH2:21][N:22]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:24](=[O:31])[C:23]2=[O:32])=[CH:18][CH:17]=1>O1CCCC1.ClCCl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:24]2([OH:31])[C:25]3[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=3)[N:22]([CH2:21][C:19]3[O:20][C:16]([C:15]([F:34])([F:33])[F:14])=[CH:17][CH:18]=3)[C:23]2=[O:32])=[C:4]([OH:8])[CH:3]=1

Participants

6

Reactant 3

HCID 115633-BromophenolHCID 673564881-((5-(Trifluoromethyl)furan-2-yl)methyl)indoline-2,3-dioneHCID 178418918HCID 178418918, compound

Product 1

HCID 673570703-(4-bromo-2-hydroxyphenyl)-3-hydroxy-1-{[5-(trifluoromethyl)furan-2-yl]methyl}-1,3-dihydro-2H-indol-2-oneYield 81%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 3-bromophenol (4.4 g, 25.4 mmol) in tetrahydrofuran (100 mL) was added iso-propylmagnesium chloride (12.7 mL, 2 M tetrahydrofuran solution, 25.4 mol) slowly at 0° C. The mixture was allowed to stir for 30 min at 0° C., then the solvent was removed in vacuo. Dichloromethane (100 mL) was added, followed by the addition of a solution of 1-((5-(trifluoromethyl)furan-2-yl)methyl)indoline-2,3-dione (5.0 g, 16.9 mol) in dichloromethane (100 mL) at 0° C. The mixture was stirred at ambient temperature for 16 h, quenched by the addition of saturated ammonium chloride solution. The organic layer was washed with water, dried over sodium sulfate and concentrated in vacuo. The obtained solid was recrystallized from ethyl acetate/hexanes to afford 3-(4-bromo-2-hydroxyphenyl)-3-hydroxy-1-{[5-(trifluoromethyl)furan-2-yl]methyl}-1,3-dihydro-2H-indol-2-one (6.4 g, 81%) as a colorless solid: 1H NMR (300 MHz, DMSO-d6) δ7.49-5.83 (m, 9H), 5.13-4.71 (m, 2H); MS (ES+) m/z 449.9 (M−17), 451.9 (M−17).

Workup

  1. customthe solvent was removed in vacuo
  2. additionDichloromethane (100 mL) was added
  3. stirringThe mixture was stirred at ambient temperature for 16 h
  4. customquenched by the addition of saturated ammonium chloride solution
  5. washThe organic layer was washed with water
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe obtained solid was recrystallized from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-9ade1adde748463f81fda8679d322fa5
Source dataset
uspto-grants-2014_12
Patent number
US08916580B2

Reaction notes

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